Prostate cancer is the most common malignancy and second cause of cancer death in males in the United States. In most cases, death results within about 1 year from progression to hormone-refractory (HRPC) metastatic disease, which is often attended by severe bone pain due to metastasis. No form of post-hormonal manipulative therapy has yet been definitively demonstrated to prolong survival. Exploratory treatment approaches are highly justified to attempt to identify more effective agents. This is a single-arm Phase II study to evaluate the response rate of patients with metastatic (M1/D1-2 disease) hormone refractory prostate cancer to intravenous arsenic trioxide therapy. This is a collaborative study between the Montefiore Medical Center, Bronx, New York and the Mount Sinai Medical Center, New York, New York. It will have a standard two-stage accrual design for early termination in the event of insufficient ageny efficacy.